Cardiac involvement in rheumatoid arthritis (RA) is uncommon and often clinically silent, but may encompass valvular, structural, and conduction system abnormalities. Involvement of the mitral-aortic intervalvular fibrosa (MAIVF) and the membranous interventricular septum is exceptionally rare and has not been previously described in RA. A 61-year-old man with longstanding seropositive RA presented with syncope due to intermittent complete atrioventricular block. Multimodality imaging revealed severe degenerative mitral regurgitation, moderate-to-severe aortic regurgitation, a pseudoaneurysm of the MAIVF extending into the left ventricular outflow tract, and a membranous interventricular septal aneurysm. Infective and congenital etiologies were excluded by repeated negative blood cultures, 18F-FDG PET, and comprehensive imaging. The patient underwent successful surgical mitral and aortic valve replacement. Histopathological analysis demonstrated rheumatoid nodules within both excised valves, confirming immune-mediated valvular involvement. Persistent conduction abnormalities required permanent pacemaker implantation. This report describes the first documented case of a MAIVF pseudoaneurysm in a patient with RA, associated with multivalvular disease and high-grade conduction disturbance. The findings highlight the potential for severe, atypical cardiac manifestations of RA in the absence of active systemic inflammation and underscore the pivotal role of multimodality imaging and multidisciplinary evaluation in establishing diagnosis and guiding management.

B cells play essential roles in adaptive immunity by producing antigen-specific antibodies and interacting with T cells. Single-cell RNA and BCR sequencing technologies have enabled high-resolution dissection of B cell heterogeneity across diverse disease contexts. Atypical B cells (ABCs) display complex and critical functions in human immunity, yet their transcriptional heterogeneity, BCR diversity, and context-specific roles remain incompletely understood.

Intraoperative frozen-section (FS) margin assessment is essential for guiding precise resection in perihilar cholangiocarcinoma (pCCA). However, freezing artifacts, superficial sampling, drainage-related reactive epithelial changes, and subtle cytologic atypia in well-differentiated adenocarcinoma can make intraoperative interpretation difficult. We report a 70-year-old woman with Bismuth-Corlette type II pCCA who underwent radical extrahepatic bile duct resection after PTBD-mediated biliary decompression. Intraoperative FS of the distal bile duct margin showed atypical glands of undetermined nature, while proximal margins were negative. Because additional caudal resection would probably have required combined pancreaticoduodenectomy in an elderly patient recovering from severe obstructive jaundice, the surgical team avoided extended resection after real-time surgical-pathological discussion. Permanent sections and immunohistochemistry subsequently confirmed well-differentiated adenocarcinoma involving the distal margin, perineural invasion, and regional lymph-node metastasis, consistent with an unintended R1 resection. This case illustrates that an indeterminate FS margin should be regarded as a high-risk gray-zone finding rather than a safe negative result. We propose a three-tier margin risk-stratification framework in which a "presumed positive" principle triggers repeat oriented sampling, intraoperative multidisciplinary consultation, and individualized balancing of oncologic radicality against physiological reserve. When aggressive resection is contraindicated, meticulous documentation, early adjuvant therapy, and rigorous long-term surveillance are essential.

Epstein-Barr virus (EBV) infection is highly prevalent worldwide, and its seroepidemiology varies according to age and sociodemographic factors. Recent observations suggest potential shifts in exposure dynamics following the COVID-19 pandemic and ongoing challenges in interpreting atypical antibody profiles. This retrospective study evaluated EBV serological patterns in 11,503 patients tested VCA IgM, VCA IgG, EA IgG, and EBNA IgG between January 2023 and August 2025 at a tertiary-care hospital. Patterns were classified as seronegative, primary infection, past infection, reactivation pattern, or atypical. Age- and sex-related distributions were analyzed using logistic regression. Past infection was the most frequent profile (64.0%), followed by seronegativity (19.8%) and atypical patterns (14.3%). VCA IgG seropositivity reached 53.2% in the 5-9 age group and increased with age. Age was strongly associated with EBV seropositivity, and female sex independently increased the odds of VCA IgG positivity. Atypical serological patterns were more common in younger individuals and showed an inverse association with age, while sex had no independent effect. Isolated VCA IgG positivity was the most common atypical pattern. These findings provide updated data on EBV serological patterns in a large tertiary-care cohort during the post-pandemic period. The observed age-specific seropositivity rates may suggest a trend toward later EBV exposure; however, the absence of a direct pre-pandemic comparator requires cautious interpretation. Accurate interpretation of atypical EBV serological profiles remains important in clinical practice and should consider patient age, timing of antibody responses, and analytical characteristics of the assay.

Behçet's disease (BD) is a complex, relapsing multisystem disorder characterized by autoinflammatory features. Because disease-specific diagnostic biomarkers are lacking and clinical presentation varies according to geographic background and organ involvement, diagnosis may be delayed, particularly in non-endemic regions and in patients with atypical manifestations. Therapeutic management is highly individualized and guided by disease severity and dominant organ involvement. Severe, refractory, or organ-threatening disease often requires aggressive immunosuppressive treatment, including targeted biologic therapy with monoclonal anti-tumor necrosis factor (anti TNF) alpha agents such as infliximab and adalimumab. Therapeutic drug monitoring (TDM), based on serum trough drug concentrations and anti-drug antibodies, is routinely used to optimize anti-TNF therapy in inflammatory bowel disease and is increasingly discussed in other immune-mediated inflammatory diseases treated with monoclonal antibodies. In Behçet's disease, however, TDM is not yet standard practice, and Behçet-specific therapeutic trough targets for infliximab and adalimumab have not been validated. Nevertheless, integrating TDM with clinical assessment may support more individualized decision-making by helping distinguish insufficient drug exposure, immunogenicity, and pharmacodynamic failure. In this article, we discuss the rationale for TDM in anti-TNF-treated BD, summarize the current direct and indirect evidence, and propose a cautious, clinically guided approach. Behçet's disease; infliximab; adalimumab; anti-TNF therapy; therapeutic drug monitoring; trough levels; anti-drug antibodies; treatment optimization.

A woman in her late 40s presented with a 1 year history of progressive symmetrical rest tremor, bradykinesia, rigidity, hypophonia and postural instability (Movement Disorder Society-sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III 41) without musculoskeletal symptoms or family history. Routine investigations were unremarkable except low-normal serum alkaline phosphatase (41 U/L, range 35-104), mild anaemia and vitamin D insufficiency; brain MRI showed blooming in bilateral globus pallidi. Minimal to no improvement observed at 1 month on modest dopaminergic dosing (MDS-UPDRS III 38). Whole-exome sequencing identified a heterozygous pathogenic frameshift variant c.388del (p.Val130Cysfs*1) in ALPL (alkaline phosphatase, liver/bone/kidney) gene. In the absence of classical skeletal features and without substrate testing, this finding is suggestive of a possible mild adult hypophosphatasia phenotype. This case highlights a potential association between ALPL variants and parkinsonism and underscores the role of genetic testing in atypical presentations.

The mitochondrial ATP synthase catalyzes the formation of ATP from ADP and Pi. In the colorless alga Polytomella parva, this enzyme displays an atypical composition in the subunits that build the peripheral arm and in the ones involved in its dimerization. In addition to ten extra subunits (Asa1-10) apparently absent from other ATP synthases, the catalytic α and β subunits possess amino-acid extensions in their N- and C-terminal regions, respectively. The δ subunit-homologous to the bacterial ε subunit and responsible for linking the hydrophilic and hydrophobic sectors of the enzyme-also contains an atypical N-terminal extension. The ATP synthase of P. parva appears to lack an IF1 peptide, the natural inhibitor of ATP hydrolysis. Due to the potential closeness of the δ subunit N-terminal extension to the DELSEED region of the catalytical core of the enzyme, we hypothesized that the δ subunit could regulate the hydrolytic activity of the algal ATP synthase and evaluated this possibility experimentally. We also investigated whether the S. cerevisiae IF1 polypeptide could exert a cross-species inhibitory effect on the algal enzyme. Biochemical results, complexome profiling analysis, and 3D-structural data indicate the absence of a peptide with inhibitory capabilities in the algal ATP synthase and suggest that the enzyme hydrolytic activity may be regulated by ADP levels.

Unsupervised self-administered cleansing enemas pose a rare but catastrophic risk of colorectal perforation. We report a 71-year-old man presenting with acute peritonitis immediately after a self-enema for chronic constipation. Notably, he connected the enema hose directly to a household water tap, inadvertently introducing a large volume of water under high mains pressure. Radiography revealed pneumoperitoneum. Emergency laparotomy identified a 5-cm longitudinal blowout perforation on the mesenteric border of the sigmoid colon with fecal contamination. A Hartmann-type procedure (partial sigmoid resection with an end colostomy) was performed. Histopathology confirmed a structurally normal colonic wall devoid of underlying pathologies. The findings were consistent with massive hydrostatic pressure injury, likely exacerbated by distal fecal loading. The patient recovered uneventfully, with no complications at the 30-day follow-up. This case highlights the extreme danger of connecting enema devices directly to domestic water supplies and emphasizes prompt surgery for atypical barogenic perforations.